KIF5A mutations causing hereditary spastic paraplegia and Charcot-Marie-Tooth disease (CMT), a heterogeneous group of inherited peripheral neuropathies, are primarily missense mutations clustered in the N-terminal motor domain, whereas mutations causing ALS occur in the C-terminal cargo-binding domain, suggesting that disruption of different aspects of kinesin function underlies specificity of distinct neurodegenerative diseases (59). This evidence concerns the gene KIF5A and amyotrophic lateral sclerosis.